Iatrogenic complications of steroid therapy

Question 1

Cortisol is converted to cortisone in

Answer 1

the kidney by 11-beta hydroxysteroid dehydrogenase 2

Question 2

Cortisone is converted to cortisol in

Answer 2

the liver by 11-beta hydroxysteroid dehydrogenase 1

Question 3

What is the half-life of cortisol?

Answer 3

30 minutes for original cortisol, ~90 mins of regenerated cortisol from cortisone

Question 4

What is the course of cortisol replacement therapy?

Answer 4

cortisol (hydrocortisone) or cortisone tablets, short half-life (requires a few doses throughout the day, best to mimic physiological time course ie peak in early morning and with meals); extra doses (2-3x as much) are required during infections or periods of stress

Question 5

What are the iatrogenic complications of glucocorticoid therapy?

Answer 5

cushingoid syndrome; adrenal suppression; immunosuppression (reactivation of latent infections eg TB); peptic ulcers (commonly prescribed with NSAIDs); osteoporosis; inhibition of linear growth in children

Question 6

What are the features of Cushingoid syndromes?

Answer 6

weight gain, muscle wasting, skin thinning, bone wasting, hyperglycaemia, hypertension (salt and water retention), inhibition of linear growth, moon face, red cheeks, fat pads, striae, bruisability, poor wound healing

Question 7

What are the two types of action of glucocorticoids?

Answer 7

Transactivation (activation of gene transcription via GREs), and transrepression (reduction of gene transcription via inhibition of AP-1 and NF-kB)

Question 8

What is the major complication of glucocorticoid therapy?

Answer 8

Adrenal suppression, often involving atrophy of the gland

Question 9

How is adrenal suppression avoided in glucocorticoid therapy?

Answer 9

allowing the hypothalamus to release ACTH and stimulate adrenals (preventing atrophy) by avoiding long-lasting drugs, using alternate day dosing, and ensuring low levels of the exogenous steroid when ACTH is low (early morning); mimimizing absorption (inhalation or topical); third generation glucocorticoid drugs

Question 10

Ciclesonide

Answer 10

third generation glucocorticoid, inhaled, used for asthma; it is a pro-drug activated in the lungs rather than the mouth or larynx; because it is lipophilic it is retained in tissues rather than the circulation (reduces absorption); low bioavailability bc metabolised in liver first pass; heavily bound in blood by proteins which lowers concentration

Question 11

What is the aim of third generation glucocorticoids like ciclesonide?

Answer 11

Reduce systemic absorption of steroids to prevent adrenal suppression

Question 12

How do glucocorticoids decrease bone density?

Answer 12

upregulation of RANKL, the ligand that activates osteoclast precursors, and downregulation of OPG, an antibody ligand that blocks RANKL from activating osteaoclasts - tf get more osteoclasts and more bone breakdown